On June 12, 2020 AstraZeneca reported that Detailed results from both the Phase II ACE-CL-001 trial and the pivotal Phase III ASCEND trial showed the long-term efficacy and tolerability of Calquence (acalabrutinib) in chronic lymphocytic leukaemia (CLL), one of the most common types of adult leukaemia.1,2,3 (Press release, AstraZeneca, JUN 12, 2020, View Source [SID1234561024])

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The results will be presented during the Virtual Edition of the 25th European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress, 11 to 14 June 2020.

In the single-arm ACE-CL-001 trial, 86% of CLL patients treated with Calquence as a 1st-line monotherapy remained on treatment at a median follow up of more than four years. The trial showed an overall response rate of 97% (7% complete response; 90% partial response) and a 100% overall response rate in subgroups of patients with high-risk disease characteristics, including genomic aberrations (17p deletion and TP53 mutation), immunoglobulin mutation status (unmutated IGHV), and complex karyotype. Safety findings showed no new long-term issues.1,4

In the final analysis of ASCEND, an estimated 82% of patients with relapsed or refractory CLL treated with Calquence remained alive and free from disease progression at 18 months compared with 48% of patients on rituximab combined with idelalisib or bendamustine.2 The trial previously met the primary endpoint of Independent Review Committee-assessed progression-free survival at the interim analysis.5

Richard R. Furman, Director of the CLL Research Center, Weill Cornell Medicine said: "These data demonstrate no new safety concerns for acalabrutinib, confirming its ability to safely provide meaningful, long-term clinical benefit for patients with treatment-naive and relapsed or refractory disease. The safety profile of acalabrutinib makes treatment to progression an important and plausible option for patients."

José Baselga, Executive Vice President, Oncology R&D said: "These long-term data reaffirm that Calquence delivers a durable response with a favourable safety profile for chronic lymphocytic leukaemia patients. Patients with chronic lymphocytic leukaemia are typically 70 years or older with comorbidities and often require treatment over a long time, making the sustained safety and efficacy profile highly relevant to their quality of life."

Results from the Phase II ACE-CL-001 trial informed the development of the pivotal Phase III ELEVATE TN trial, which, along with findings from the Phase III ASCEND trial, formed the basis for the US approval of Calquence for the treatment of patients with CLL or small lymphocytic lymphoma (SLL).

Calquence in previously untreated CLL: 4.4-year follow-up from Phase II trial (abstract #S163)

The Phase II ACE-CL-001 trial investigated safety and efficacy of Calquence (100mg twice-daily [n=62] or 200mg once-daily [n=37]) in previously untreated patients with CLL.1 On 1 May 2015, patients receiving the 200mg dosing regimen were switched to the 100mg regimen.1

Key data from the Calquence Phase II ACE-CL-001 trial1

Calquence Phase II ACE-CL-001 trial table
CI, confidence interval; CR, complete response; DoR, duration of response; EFS, event free survival; TTR, time to response; NR, not reached; ORR, overall response rate; PR, partial response

Response rates were 100% in each subgroup of patients with high-risk disease characteristics (unmutated IGHV [n=57], 17p deletion [n=9], TP53 mutation [n=9], and complex karyotype [n=12]), and reduction in lymph node disease was noted in all patients tested (n=97).1

At the time of data cut-off, 85 (86%) patients receiving Calquence remained on treatment. Six patients discontinued treatment due to adverse events (AEs) and three patients discontinued for progressive disease (PD). No patient discontinued Calquence due to bleeding events, hypertension, or atrial fibrillation. Incidence of AEs generally diminished with time on the trial. The most common AEs (≥40%) of any grade in the trial were diarrhoea (52%), headache (45%), upper respiratory tract infection (44%), arthralgia (42%), and contusion (42%). All-grade and Grade ≥3 events of clinical interest included infection (84% and 15%, respectively), bleeding events (66%, 3%), hypertension (22%, 11%), leukopenia (9%, 9%), and thrombocytopenia (3%, 1%). Atrial fibrillation (all grades) occurred in 5% of patients with Grade ≥3 occurring in 2%. Second primary malignancies (SPM) excluding non-melanoma skin (all grades) occurred in 11% of patients.1 Serious adverse events (SAEs) were reported in 38% of patients. SAEs occurring in more than two patients included pneumonia (n=4) and sepsis (n=3).1

Final results of Calquence Phase III ASCEND trial in relapsed or refractory CLL (abstract #S159)

ASCEND was a global, randomised, multicentre, open-label, Phase III trial that investigated the efficacy and safety of Calquence (100mg twice-daily) versus investigator’s choice of rituximab combined with idelalisib (IdR) or bendamustine (BR) in patients with relapsed or refractory CLL.2

Key data from the final analysis of the Calquence Phase III ASCEND trial2

Calquence Phase III ASCEND trial table
BR, rituximab in combination with bendamustine; CI, confidence interval, DoR, duration of response; HR, hazard ratio; IdR, rituximab in combination with idelalisib; INV, investigator; NR, not reached; ORR, overall response rate; OS, overall survival; PFS, progression-free survival

Sixteen per cent of patients on Calquence, 56% of patients on IdR, and 17% of patients on BR discontinued treatment because of AEs. Common AEs occurring in greater than 15% of patients of any grade in the Calquence arm of the trial included headache (22%), neutropenia (21%), diarrhoea (20%), upper respiratory tract infection (20%), cough (16%), and anaemia (16%). Events of clinical interest for Calquence versus controls included atrial fibrillation (all grade, 6% and 3%, respectively), major haemorrhage (all grade, 3% in both arms), infections (Grade ≥3, 20% and 25%, respectively), and SPM excluding non-melanoma skin cancer (all grade, 5% and 2%, respectively). SAEs (any grade) occurred in 33% of patients receiving Calquence, 56% of IdR patients, and 26% of BR patients.2

Chronic lymphocytic leukaemia

Chronic lymphocytic leukaemia (CLL) is one of the most common types of leukaemia in adults, with an estimated 105,000 new cases globally in 2016 and 21,040 new cases in the US in 2020, and the number of people living with CLL is expected to grow with improved treatment as patients live longer with the disease.3,6,7,8 In CLL, too many blood stem cells in the bone marrow become abnormal lymphocytes and these abnormal cells have difficulty fighting infections.3 As the number of abnormal cells grows there is less room for healthy white blood cells, red blood cells, and platelets.3 This could result in anaemia, infection, and bleeding.3 B-cell receptor signalling through Bruton’s tyrosine kinase is one of the essential growth pathways for CLL.

Calquence

Calquence (acalabrutinib) is a next-generation, selective inhibitor of Bruton’s tyrosine kinase (BTK). Calquence binds covalently to BTK, thereby inhibiting its activity.4,9 In B-cells, BTK signaling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion.4

Calquence is approved for the treatment of adult patients with chronic lymphocytic leukaemia (CLL) in nine countries and for adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy in 14 countries. The US MCL indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. As part of an extensive clinical development programme, AstraZeneca and Acerta Pharma are currently evaluating Calquence in 23 company-sponsored clinical trials. Calquence is being developed for the treatment of multiple B-cell blood cancers including CLL, MCL, diffuse large B-cell lymphoma, Waldenström macroglobulinaemia, follicular lymphoma, and other haematologic malignancies.

AstraZeneca in haematology

Leveraging its strength in oncology, AstraZeneca has established haematology as one of four key oncology disease areas of focus. The Company’s haematology franchise includes two US FDA-approved medicines and a robust global development programme for a broad portfolio of potential blood cancer treatments. Acerta Pharma serves as AstraZeneca’s haematology research and development arm. AstraZeneca partners with like-minded science-led companies to advance the discovery and development of therapies to address unmet need.

AstraZeneca in oncology

AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With six new medicines launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers. In addition to AstraZeneca’s main capabilities, the Company is actively pursuing innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by the investment in Acerta Pharma in haematology.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

On June 11, 2020 Avalon GloboCare Corp. (NASDAQ: AVCO), a clinical-stage global developer of cell-based technologies and therapeutics, reported that it has entered into a three-way material transfer agreement (MTA) with Weill Cornell Medicine in New York City and the Company’s strategic partner, Arbele Limited (Press release, Avalon, JUN 11, 2020, View Source [SID1234609547]).

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With this agreement, Avalon GloboCare Corp. and Arbele Limited intend to collaborate with Weill Cornell Medicine and co-develop the standardized laboratory steps necessary to generate clinical-grade CAR-T and CAR-NK cells for use in future human clinical trials with Avalon’s first FLASH-CAR(TM) platform candidate, AVA-011. This step, called process development, will provide the bridge between Avalon’s benchtop research and the bio-manufacturing processes to potentially deliver the clinical-grade cellular immunotherapy product to patients.

"We are excited about this agreement to translate our cellular therapy candidates into standardized, clinical-grade cell products that could be used in future clinical trials. This step reflects our dedication to establishing an infrastructure to develop our cellular immunotherapy candidates and to maintain the highest possible standards for generating clinical-grade cells for human cancer trials," stated David Jin, M.D., Ph.D., President and Chief Executive Officer of Avalon GloboCare.

AVA-011 is a next generation cellular immunotherapy candidate using Avalon’s FLASH-CAR(TM) that targets both CD19 and CD22 tumor antigens on cancer cells. Avalon has already successfully completed pre-clinical research on AVA-011, including tumor cytotoxicity studies. (See May 8, 2020 press release, ‘Avalon GloboCare Advances Next Generation Cellular Immunotherapy with FLASH-CAR(TM) Technology for Blood Cancers’)

Avalon’s next generation immune cell therapy using FLASH-CAR(TM) technology is being co-developed with the Company’s strategic partner Arbele Limited. The adaptable FLASH-CAR(TM) platform may be used to create personalized cancer cell therapy from a patient’s own cells, as well as off-the-shelf cell therapy from a universal donor, expanding the reach of cancer patients that could be treated.

On June 11, 2020 Travecta Therapeutics reported it has raised an additional $12 million in financing, closing its Series A round at a total of $27 million (Press release, Travecta Therapeutics, JUN 11, 2020, View Source [SID1234605570]). The fund-raise was led by TKS1, a life science focused venture capital fund formed by the partnership between SPRIM and Tikehau Capital.

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"The positive traction we are having with our data along with the strength of interest from development and licensing partners has motivated our current investors to contribute an additional $12 million," said Michael Shleifer, CEO of Travecta Therapeutics. "This financing will accelerate our trajectory into the next phase of development, and we’re thankful to our partners for the support."

This funding comes on the heels of Travecta Therapeutics’ mVECTATM platform achieved targeting of a broad range of product candidates across the blood-brain-barrier with proven efficacy against pharmacological targets. "Our mVECTATM platform technology is unlocking key biological targets in neurological diseases that were previously difficult to engage because of the blood-brain barrier," said Dr. Mahmood Ahmed, Chief Scientific Officer.

The proceeds from the Series A financing will be used to support Travecta’s growth and advance the development of TVT-004, Travecta’s lead non-opioid product targeting pain. The company plans to enter clinical trials in 2021. The funding will also support the progression of the company’s earlier stage research programs in neuro-oncology and neuro-inflammation.

Bruno de Pampelonne, Chairman of Tikehau IM said, "Travecta Therapeutics’ mVECTATM platform could revolutionize treatments in a broad range of neurological indications often very difficult to treat. We are thrilled to partner with Travecta’s team in this endeavor"

On June 11, 2020 Invitae reported that New recommendations from a large, multidisciplinary consensus conference published this week in the Journal of Clinical Oncology suggest expanding use of genetic testing to guide treatment for men with prostate cancer, including the use of panel testing and testing patients with early stage disease (Press release, Invitae, JUN 11, 2020, View Source [SID1234561384]). Taken together with research recently presented by Invitae (NYSE: NVTA), a leading genetics company, the publications underscore the utility of increased access to genetic testing for men with prostate cancer across all stages of disease.

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Invitae’s (NVTA) mission is to bring comprehensive genetic information into mainstream medical practice to improve the quality of healthcare for billions of people. www.invitae.com (PRNewsFoto/Invitae Corporation)

Invitae was among the non-voting sponsors of the conference, which gathered more than 100 experts across a number of specialties with the goal of developing recommendations for how clinicians can use genetic testing to help patients benefit from precision medicine approaches to prostate cancer.

"Inherited prostate cancer is starting to get the attention it deserves, but we have a long way to go to catch up to the research and testing that has been done in other cancers, such as breast cancer," said Sarah Nielsen, M.S., L.C.G.C. a medical affairs liaison now at Invitae who previously participated in the conference. "This framework provides a very thoughtful approach to implementing genetic testing for prostate cancer treatment, screening and family testing. Importantly, the framework recognizes that changes in a number of different genes can increase prostate cancer risk and therefore encourages greater use of panel testing for men with metastatic disease. With new precision therapies linked to specific genetic changes, increased genetic testing can help identify patients who could benefit from these approaches."

Among the consensus conference recommendations:

Larger panels are useful for patients with metastatic disease

Large germline panels and somatic testing were recommended for patients with metastatic prostate cancer. Of the approximately 12-17% of men with metastatic prostate cancer who harbor germline variants, the majority are found in DNA damage repair (DDR) genes such as BRCA1, BRCA2, ATM, CHEK2, PALB2, and the DNA mismatch repair (MMR) genes. Large panels provided information across these and other genes of significance, information which is increasingly informing options for PARP inhibitors, immune checkpoint inhibitors, platinum chemotherapy, and clinical trials.

Genetic information can support early diagnosis and inform disease surveillance

Germline test results are increasingly important for early detection, as men with BRCA2 variants exhibit higher rates of prostate cancer, often with a younger age at diagnosis and more clinically significant disease. Among patients with early-stage disease, emerging data suggest that men with germline BRCA2 mutations and possibly ATM mutations have higher rates of upgrading of prostate biopsies while on active surveillance, suggesting the utility of genetic information in shaping surveillance strategies after diagnosis.

Importance of using genetic information requires novel strategies to increase access to counseling resources

The guidelines recommend broad access to genetic counseling support but shortages of genetic counselors and wait times for traditional genetic counseling workflows will require development of alternate models for timely and responsible delivery of genetic testing for men and their families. The consensus framework provides suggestions for clinicians on how to counsel and provide alternatives to traditional in-person appointments for patients across a number of issues related to testing, including using pretest education materials and the use of telehealth genetic counseling sessions.

"This framework provides an important step in helping clinicians incorporate genetic testing into care for a wide range of prostate cancer patients," said Robert Nussbaum, M.D., chief medical officer of Invitae. "Research has shown that narrow testing criteria will miss men with clinically relevant variants that could inform their care. Providing a framework for more clinicians to expand their use of genetic testing will increase the number of patients who benefit from precision medicine approaches."

Research underscores frequency of clinically important variants that may be missed by narrow testing criteria

In addition, a study presented recently at the American College of Medical Genetics and Genomics online annual meeting that further underscored the frequency of actionable variants expanded testing can help uncover.

The study of 2,252 men who participated in Invitae’s Detect Prostate Cancer program found an overall positive rate of 13% with no statistical differences in rates among stages of disease. Only half of patients with an actionable variant reported a family history suggestive of increased risk. Nearly three-quarters (71%) of positive patients were eligible for management guidelines and/or potentially eligible for approved precision therapies or clinical trials. These data suggest that broader testing criteria and greater access to testing leads to better informed care for patients and their families.

The consensus conference noted the need for additional research into the associations between genetics and prostate cancer in African-American men, who are 1.8 times more likely to be diagnosed with and 2.2 times more likely to die from prostate cancer. Importantly, this study included 16% participation among African-Americans, which is greater participation than previous similar studies, aligning to the consensus conference research priorities.

The full consensus statement can be found in the Journal of Clinical of Oncology.

On June 11, 2020, Mustang Bio, Inc. ("Mustang" or the "Company") reported that it has entered into an underwriting agreement (the "Underwriting Agreement") with Cantor Fitzgerald & Co., as representative of the underwriters named therein (each, an "Underwriter" and collectively with Cantor Fitzgerald & Co., the "Underwriters") (Filing, 8-K, Mustang Bio, JUN 11, 2020, View Source [SID1234561090]). Pursuant to the Underwriting Agreement, the Company agreed to sell to the Underwriters, in a firm commitment underwritten public offering, 10,769,231 shares (the "Firm Shares") of the Company’s common stock, $0.0001 par value per share ("Common Stock"), at a price to the public of $3.25 per share, less underwriting discounts and commissions. In addition, pursuant to the Underwriting Agreement, the Company has granted the Underwriters an option, exercisable for 30 days, to purchase up to an additional 1,615,384 shares of Common Stock (the "Additional Shares," together with the Firm Shares, the "Shares"). The transactions contemplated by the Underwriting Agreement are expected to close on June 15, 2020, subject to the satisfaction of customary closing conditions. A copy of the Underwriting Agreement is attached hereto as Exhibit 1.1 and is incorporated by reference herein.

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Cantor Fitzgerald & Co. is acting as sole book-running manager for the offering. Oppenheimer & Co. Inc. is acting as lead manager for the offering.

The gross proceeds to the Company are expected to be approximately $35 million, assuming no exercise of the option to purchase Additional Shares and excluding underwriting discounts and commissions and other offering-related expenses.

The Underwriting Agreement contains customary representations, warranties and agreements by the Company, customary conditions to closing, indemnification obligations of the Company and the Underwriters, including for liabilities under the Securities Act of 1933, as amended (the "Securities Act"), other obligations of the parties and termination provisions.

The offering is being made pursuant to the Company’s effective "shelf" registration statements on Form S-3 (File Nos. 333-226175 and 333-233350) (the "Registration Statements") filed with the Securities and Exchange Commission (the "SEC") and declared effective by the SEC on July 27, 2018 and September 30, 2019, respectively, as supplemented by a preliminary prospectus supplement filed with the SEC on June 10, 2020 and a final prospectus supplement filed with the SEC on June 12, 2020, pursuant to Rule 424(b) under the Securities Act.

Alston & Bird LLP, counsel to the Company, delivered an opinion as to the validity of the Shares, a copy of which is attached hereto as Exhibit 5.1 and is incorporated by reference herein.

This Current Report on Form 8-K is being filed to incorporate the Underwriting Agreement and opinion by reference into such Registration Statements. The foregoing summary description of the offering and the documentation related thereto, including without limitation, the Underwriting Agreement, does not purport to be complete and is qualified in its entirety by reference to such Exhibits.

The Underwriting Agreement has been included to provide investors and security holders with information regarding its terms. It is not intended to provide any other factual information about the Company. The representations, warranties and covenants contained in the Underwriting Agreement were made only for purposes of such agreement and as of specific dates, were solely for the benefit of the parties to such agreement, and may be subject to limitations agreed upon by the contracting parties, including being qualified by confidential disclosures exchanged between the parties in connection with the execution of the Underwriting Agreement. The representations and warranties may have been made for the purposes of allocating contractual risk between the parties to the agreement instead of establishing these matters as facts, and may be subject to standards of materiality applicable to the contracting parties that differ from those applicable to investors. Investors are not third-party beneficiaries under the Underwriting Agreement and should not rely on the representations, warranties and covenants or any descriptions thereof as characterizations of the actual state of facts or condition of the Company or any of its subsidiaries or affiliates. Moreover, information concerning the subject matter of the representations and warranties may change after the date of the Underwriting Agreement, and this subsequent information may or may not be fully reflected in the Company’s public disclosures.